This research will study the mechanism(s) and cellular basis of the spontaneous occurrence of autoantiIgG antibodies in aged mice and human subjects. The manipulation of this response through the immune functional network and particularly by antidiiotype antibodies against antiallotyupe antibodies will be suited. The 129/sv mice strain shows an age-associated occurrence of an autoantiallotype response. We will investigate in this strain, the presence of T helper (TH) and T suppressor (TS) cells which necessarily participate in the mounting and regulating the autoantiallotype response. It appears that TH cells specific for the a allelic form of IgG2a should be required for the synthesis of autoantiallotype antibodies in aged mice. By contrast, putative TS cells could control, in the young mice, either the activity of TH cells or of B silent clone(s) having the potential to participate in the synthesis of antiallotype antibody. The effects of an infectious agent which can pass horizontally to clean mice and which can be responsible for the autoimmune response will also be investigated. In humans, we will investigate the effects of autoantiIgG antibodies (rheumatoid factor) on functions of T and B cells of young and old subjects as well as the role of various regulatory T cells. The effects of antiId antisera against antiIgG antibodies (i.e. antiIgG2a allotype antibodies in mice and antiIgG-rheumatoid factor in man) on the function of T and B lymphocytes involved in the antoantiIgG response will be also studied in view to prevent the occurrence or to inhibit the development of this autoimmune response.